IL23R (Interleukin-23 receptor) variants and mutations
IL23R (also known as Interleukin-23 receptor) is a human protein-coding gene encoding an interleukin-23 receptor protein. It enables lymphocytes to respond to IL-23 and maintain Th17-type inflammatory programs. Common variants can strongly modify inflammatory bowel disease risk, and therapeutic interruption of IL-23 signaling is effective in several immune-mediated disorders. This analysis covers 888 IL23R variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes inflammatory bowel disease, psoriasis, and Crohn disease. Example IL23R variants include N2D, N2T, and N2N.
Variant analysis overview
- Gene: IL23R
- Protein: Interleukin-23 receptor
- UniProt accession: Q5VWK5
- Organism: Homo sapiens
- Variants analyzed: 888
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 678 unspecified-consequence records; 78 synonymous variants; 8 stop-gained variants; 113 missense variants; 5 frameshift variants; 3 splice-region variants; 3 in-frame deletions; 1 in-frame insertions
- Prediction scores: 666 variants have prediction scores (75% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: inflammatory bowel disease, psoriasis, Crohn disease, ulcerative colitis, enteritis, ankylosing spondylitis, sarcoidosis, colitis, psoriasis vulgaris, autoimmune disease, skin disorder, ulcerative proctosigmoiditis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 domains; 8 post-translational modification sites.
- Structural context: 342 variants have structural context.
- PTM context: 13 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable IL23R variants
Examples include N2D, N2T, N2N, Q3H, Q3R, V4A, V4S, V4D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- N2D (p.Asn2Asp), ExAC rs746445795, gnomAD rs746445795, REVEL 0.24, CADD 17.40
- N2T (p.Asn2Thr), Ensembl rs2102553708
- N2N (p.Asn2Asn), rs1367289249, gnomAD 1-67168126-T-C, CADD 1.46
- Q3H (p.Gln3His), rs1884444, ClinGen CA899612, ClinVar RCV001520832, ClinVar RCV003487397, REVEL 0.13, CADD 9.98, Benign, not specified; not provided
- Q3R (p.Gln3Arg), rs756938673, ClinGen CA899611, ClinVar RCV003819801, ExAC rs756938673, REVEL 0.11, CADD 8.92, Uncertain significance, not provided
- V4A (p.Val4Ala), ExAC rs111257711, gnomAD rs111257711
- V4S (p.Val4Ser), gnomAD 1-67168129-G-GTCA, CADD 23.00
- V4D (p.Val4Asp), gnomAD 1-67168131-T-A, REVEL 0.51, CADD 21.70
- V4V (p.Val4Val), gnomAD 1-67168132-C-T, CADD 3.61
- T5A (p.Thr5Ala), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- T5N (p.Thr5Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I6S (p.Ile6Ser), ExAC rs770324228, TOPMed rs770324228, gnomAD rs770324228, REVEL 0.22, CADD 3.61, Uncertain significance, not specified
- I6V (p.Ile6Val), gnomAD 1-67168136-A-G, REVEL 0.12, CADD 0.04
- Q7* (p.Gln7Ter), NCI-TCGA Cosmic COSV6137, CADD 7.35, Variant assessed as somatic; high impact.
- Q7K (p.Gln7Lys), gnomAD 1-67168139-C-A, REVEL 0.46, CADD 18.80
- Q7R (p.Gln7Arg), gnomAD 1-67168140-A-G, REVEL 0.38, CADD 18.60
- W8* (p.Trp8Ter), TOPMed rs1462863162, CADD 35.00
- D9E (p.Asp9Glu), rs144070297, ClinGen CA899616, ClinVar RCV001982463, ESP rs144070297, REVEL 0.16, CADD 0.05, Uncertain significance, not provided
- D9N (p.Asp9Asn), ExAC rs775994483, gnomAD rs775994483, REVEL 0.29, CADD 20.70
- D9V (p.Asp9Val), TOPMed rs1215777747, gnomAD rs1215777747, REVEL 0.47, CADD 19.90
- D9H (p.Asp9His), gnomAD 1-67168145-G-C, REVEL 0.21, CADD 16.30
- D9G (p.Asp9Gly), gnomAD 1-67168146-A-G, REVEL 0.33, CADD 16.30
- A10T (p.Ala10Thr), rs769230441, ClinGen CA899617, ClinVar RCV003021578, ExAC rs769230441, REVEL 0.27, CADD 17.90, Uncertain significance, not provided
- A10V (p.Ala10Val), NCI-TCGA TCGA novel, REVEL 0.14, CADD 1.63, Variant assessed as somatic; moderate impact.
- A10A (p.Ala10Ala), gnomAD 1-67168150-A-G, CADD 2.34
- V11I (p.Val11Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V11L (p.Val11Leu), gnomAD rs1256418489, REVEL 0.16, CADD 0.94
- I12T (p.Ile12Thr), Ensembl rs1646896298, REVEL 0.49, CADD 16.70
- I12M (p.Ile12Met), gnomAD 1-67168156-A-G, REVEL 0.36, CADD 1.85
- I12I (p.Ile12Ile), gnomAD 1-67168156-A-T, CADD 1.53
- A13D (p.Ala13Asp), gnomAD 1-67168158-C-A, REVEL 0.54, CADD 17.90
- A13V (p.Ala13Val), gnomAD 1-67168158-C-T, REVEL 0.31, CADD 13.60
- A13A (p.Ala13Ala), gnomAD 1-67168159-C-A, CADD 0.21
- L14F (p.Leu14Phe), gnomAD rs1292287814, REVEL 0.31, CADD 6.83
- Y15C (p.Tyr15Cys), ExAC rs774581386, gnomAD rs774581386, REVEL 0.25, CADD 15.30
- Y15T (p.Tyr15Thr), gnomAD 1-67168160-CT-C, CADD 22.50
- Y15* (p.Tyr15Ter), gnomAD 1-67168165-C-A, CADD 26.50
- I16V (p.Ile16Val), rs761754539, ClinGen CA899619, ClinVar RCV002663323, ExAC rs761754539, REVEL 0.14, CADD 0.01, Uncertain significance, not provided
- I16M (p.Ile16Met), gnomAD 1-67168168-A-G, REVEL 0.34, CADD 0.30
- L17I (p.Leu17Ile), Ensembl rs1646896411, REVEL 0.16, CADD 13.30
- L17P (p.Leu17Pro), TOPMed rs1241516896, REVEL 0.70, CADD 24.20
- F18L (p.Phe18Leu), TOPMed rs1353572541, REVEL 0.27, CADD 17.90
- F18F (p.Phe18Phe), rs767807981, gnomAD 1-67168174-C-T, CADD 8.65
- S19G (p.Ser19Gly), rs185697788, ClinGen CA899621, ClinVar RCV001899118, ClinVar RCV004042641, REVEL 0.19, CADD 10.10, Uncertain significance, not specified; not provided
- S19R (p.Ser19Arg), ExAC rs760923055, gnomAD rs760923055
- W20* (p.Trp20Ter), ExAC rs765086515, TOPMed rs765086515, gnomAD rs765086515, CADD 38.00, Uncertain significance
- W20L (p.Trp20Leu), rs765086515, ClinGen CA340731863, ClinVar RCV002598359, ExAC rs765086515, REVEL 0.64, CADD 23.70, Uncertain significance, not provided
- W20R (p.Trp20Arg), rs2525198587, ClinGen CA340731861, ClinVar RCV003833297, REVEL 0.71, CADD 23.60, Uncertain significance, not provided
- C21Y (p.Cys21Tyr), gnomAD 1-67168182-G-A, REVEL 0.63, CADD 23.90
- C21C (p.Cys21Cys), rs1646896628, gnomAD 1-67168183-T-C, CADD 4.13
- H22Y (p.His22Tyr), gnomAD rs1474792230, REVEL 0.30, CADD 16.30
- H22Q (p.His22Gln), gnomAD 1-67168186-T-G, REVEL 0.44, CADD 22.10
- G23E (p.Gly23Glu), Ensembl rs1646896730
- G23R (p.Gly23Arg), ExAC rs752478137, TOPMed rs752478137, gnomAD rs752478137, REVEL 0.65, CADD 23.40
- G23G (p.Gly23Gly), gnomAD 1-67168189-A-G, CADD 21.80
- G24* (p.Gly24Ter), gnomAD 1-67168190-G-T, CADD 51.00
- G24A (p.Gly24Ala), gnomAD 1-67169342-G-C, REVEL 0.54, CADD 29.20
- G24V (p.Gly24Val), gnomAD 1-67169342-G-T, REVEL 0.60, CADD 26.80
- G24E (p.Gly24Glu), gnomAD 1-67169342-G-A, REVEL 0.70, CADD 27.50
- G24G (p.Gly24Gly), gnomAD 1-67169343-A-T, CADD 10.90
- T26A (p.Thr26Ala), TOPMed rs1290144534, gnomAD rs1290144534, REVEL 0.17, CADD 19.40
- T26K (p.Thr26Lys), gnomAD 1-67169348-C-A, REVEL 0.57, CADD 23.90
- N27S (p.Asn27Ser), gnomAD rs1465641771, REVEL 0.15, CADD 8.02
- N27N (p.Asn27Asn), rs771085299, gnomAD 1-67169352-T-C, CADD 8.04
- I28K (p.Ile28Lys), gnomAD rs1162714374, REVEL 0.69, CADD 25.20
- I28M (p.Ile28Met), gnomAD 1-67169355-A-G, REVEL 0.45, CADD 22.70
- N29T (p.Asn29Thr), gnomAD 1-67169357-A-C, REVEL 0.17, CADD 15.10
- C30F (p.Cys30Phe), NCI-TCGA Cosmic COSV6137, Variant assessed as somatic; moderate impact.
- C30S (p.Cys30Ser), gnomAD 1-67169360-G-C, REVEL 0.71, CADD 26.10
- C30Y (p.Cys30Tyr), gnomAD 1-67169360-G-A, REVEL 0.81, CADD 26.60
- G32C (p.Gly32Cys), gnomAD 1-67169365-G-T, REVEL 0.75, CADD 26.80
- G32G (p.Gly32Gly), gnomAD 1-67169367-C-T, CADD 5.28
- H33R (p.His33Arg), rs2525202689, ClinGen CA340732149, ClinVar RCV004123865, Uncertain significance, not specified
- H33H (p.His33His), rs1455151608, gnomAD 1-67169370-C-T, CADD 4.90
- H33Q (p.His33Gln), gnomAD 1-67169370-C-A, REVEL 0.10, CADD 11.20
- I34L (p.Ile34Leu), rs1156783916, ClinGen CA340732153, ClinVar RCV001986942, gnomAD rs1156783916, MutPred 0.51, Uncertain significance, not provided
- I34V (p.Ile34Val), gnomAD rs1156783916, REVEL 0.09, CADD 0.28, Uncertain significance
- I34T (p.Ile34Thr), gnomAD 1-67169372-T-C, REVEL 0.33, CADD 23.00
- I34I (p.Ile34Ile), gnomAD 1-67169373-C-A, CADD 5.69
- I34M (p.Ile34Met), gnomAD 1-67169373-C-G, REVEL 0.16, CADD 9.82
- W35* (p.Trp35Ter), rs1384135313, ClinGen CA340732163, ClinVar RCV003670497, TOPMed rs1384135313, CADD 37.00, Uncertain significance
- W35C (p.Trp35Cys), rs1396700760, ClinGen CA340732168, ClinVar RCV002296631, gnomAD rs1396700760, REVEL 0.64, CADD 26.10, Uncertain significance, not provided
- W35R (p.Trp35Arg), gnomAD 1-67169374-T-A, REVEL 0.48, CADD 22.00
- W35G (p.Trp35Gly), gnomAD 1-67169374-T-G, REVEL 0.72, CADD 25.70
- V36I (p.Val36Ile), rs2525202778, ClinGen CA340732169, ClinVar RCV003680635, Uncertain significance, not provided
- V36* (p.Val36Ter), gnomAD 1-67169374-TG-T, CADD 26.80
- V36A (p.Val36Ala), gnomAD 1-67169378-T-C, REVEL 0.64, CADD 25.30
- E37D (p.Glu37Asp), ExAC rs762697123, gnomAD rs762697123, REVEL 0.53, CADD 16.40, Likely benign
- E37E (p.Glu37Glu), rs762697123, gnomAD 1-67169382-A-G, CADD 7.70
- P38A (p.Pro38Ala), gnomAD 1-67169383-C-G, REVEL 0.69, CADD 24.00
- P38T (p.Pro38Thr), gnomAD 1-67169383-C-A, REVEL 0.69, CADD 24.30
- A39T (p.Ala39Thr), TOPMed rs1570774918, gnomAD rs1570774918, REVEL 0.43, CADD 23.90
- A39V (p.Ala39Val), Ensembl rs1646913763
- T40K (p.Thr40Lys), NCI-TCGA Cosmic COSV6137, Variant assessed as somatic; moderate impact.
- T40I (p.Thr40Ile), gnomAD 1-67169390-C-T, REVEL 0.20, CADD 15.30
- I41N (p.Ile41Asn), rs2102555960, ClinGen CA340732203, ClinVar RCV002006422, Ensembl rs2102555960, MutPred 0.75, Uncertain significance, not provided
- F42F (p.Phe42Phe), gnomAD 1-67169397-T-C, CADD 11.30
- K43E (p.Lys43Glu), gnomAD 1-67169398-A-G, REVEL 0.13, CADD 19.30
- K43N (p.Lys43Asn), gnomAD 1-67169400-G-T, REVEL 0.34, CADD 22.70
- M44T (p.Met44Thr), ESP rs144606217, ExAC rs144606217, TOPMed rs144606217, gnomAD rs144606217, REVEL 0.74, CADD 25.00, Uncertain significance, not specified
- M44V (p.Met44Val), ExAC rs763854576, gnomAD rs763854576
- G45V (p.Gly45Val), gnomAD 1-67169405-G-T, REVEL 0.78, CADD 24.90
- M46V (p.Met46Val), gnomAD rs1646913850, REVEL 0.11, CADD 5.81
- N47S (p.Asn47Ser), ExAC rs761804830, gnomAD rs761804830, REVEL 0.34, CADD 22.10
- I48V (p.Ile48Val), gnomAD 1-67169413-A-G, REVEL 0.23, CADD 10.30
- S49Y (p.Ser49Tyr), gnomAD rs1356970161, REVEL 0.71, CADD 24.80
- S49C (p.Ser49Cys), gnomAD 1-67169417-C-G, REVEL 0.62, CADD 24.90
- S49S (p.Ser49Ser), gnomAD 1-67169418-T-G, CADD 8.31
- I50M (p.Ile50Met), ExAC rs749888878, TOPMed rs749888878, gnomAD rs749888878, REVEL 0.60, CADD 22.80, Likely benign
- I50V (p.Ile50Val), rs766991367, ClinGen CA899651, ClinVar RCV003658944, ExAC rs766991367, REVEL 0.13, CADD 11.60, Uncertain significance, not provided
- I50I (p.Ile50Ile), rs749888878, gnomAD 1-67169421-A-C, CADD 7.94
- Y51H (p.Tyr51His), TOPMed rs1011510628, REVEL 0.63, CADD 23.60, Uncertain significance, not provided
- C52F (p.Cys52Phe), gnomAD rs1260672434, REVEL 0.86, CADD 26.00
- C52I (p.Cys52Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- C52Y (p.Cys52Tyr), gnomAD 1-67169426-G-A, REVEL 0.84, CADD 25.80
- A54V (p.Ala54Val), rs2525202946, ClinGen CA340732296, ClinVar RCV003678143, REVEL 0.31, CADD 22.20, Uncertain significance, not provided
- A54E (p.Ala54Glu), gnomAD 1-67169432-C-A, REVEL 0.34, CADD 15.80
- A55E (p.Ala55Glu), ExAC rs201210897, TOPMed rs201210897, gnomAD rs201210897, REVEL 0.12, CADD 11.90
- A55T (p.Ala55Thr), rs539781624, ClinGen CA899653, ClinVar RCV001368567, ExAC rs539781624, REVEL 0.08, CADD 5.87, Uncertain significance, not provided
- A55A (p.Ala55Ala), rs754273325, gnomAD 1-67169436-A-G, CADD 5.29
- I56F (p.Ile56Phe), rs767092630, ClinGen CA899656, ClinVar RCV003719794, ExAC rs767092630, REVEL 0.35, CADD 11.40, Uncertain significance, not provided
- I56S (p.Ile56Ser), TOPMed rs1646914245
- I56V (p.Ile56Val), ExAC rs767092630, TOPMed rs767092630, gnomAD rs767092630, REVEL 0.07, CADD 4.25, Uncertain significance, not provided
- K57E (p.Lys57Glu), ExAC rs779308889, gnomAD rs779308889, REVEL 0.50, CADD 25.30
- K57K (p.Lys57Lys), gnomAD 1-67169442-G-A, CADD 8.68
- N58D (p.Asn58Asp), gnomAD 1-67169443-A-G, REVEL 0.15, CADD 20.50
- N58S (p.Asn58Ser), gnomAD 1-67169444-A-G, REVEL 0.30, CADD 22.60
- N58N (p.Asn58Asn), gnomAD 1-67169445-C-T, CADD 5.11
- C59* (p.Cys59Ter), ExAC rs772622626, gnomAD rs772622626, CADD 35.00
- C59R (p.Cys59Arg), ExAC rs748673781, gnomAD rs748673781, REVEL 0.76, CADD 26.30, Uncertain significance, not provided
- Q60E (p.Gln60Glu), TOPMed rs1646914386
- Q60R (p.Gln60Arg), gnomAD 1-67169450-A-G, REVEL 0.19, CADD 20.20
- Q60Q (p.Gln60Gln), rs1179338120, gnomAD 1-67169451-A-G, CADD 7.29
- P61L (p.Pro61Leu), gnomAD rs1466428054, REVEL 0.60, CADD 23.60
- P61S (p.Pro61Ser), gnomAD rs1363189594, REVEL 0.45, CADD 22.70
- P61Q (p.Pro61Gln), gnomAD 1-67169453-C-A, REVEL 0.43, CADD 23.20
- P61P (p.Pro61Pro), rs777730388, gnomAD 1-67169454-A-G, CADD 10.40
- R62K (p.Arg62Lys), gnomAD 1-67169456-G-A, REVEL 0.20, CADD 14.00
- K63E (p.Lys63Glu), rs1469323792, ClinGen CA340732353, ClinVar RCV003846645, ClinVar RCV005587530, REVEL 0.16, CADD 14.10, Uncertain significance, not provided; not specified
- K63R (p.Lys63Arg), Ensembl rs1646914750
- K63N (p.Lys63Asn), rs1404081751, gnomAD 1-67169457-GA-G, CADD 21.30
- L64P (p.Leu64Pro), ExAC rs771174962, gnomAD rs771174962, REVEL 0.64, CADD 24.40
- L64V (p.Leu64Val), ExAC rs747027115, gnomAD rs747027115, REVEL 0.18, CADD 0.17
- H65N (p.His65Asn), ExAC rs776785412, gnomAD rs776785412, REVEL 0.20, CADD 0.20
- F66Y (p.Phe66Tyr), rs2525203117, ClinGen CA340732375, ClinVar RCV002715924, Uncertain significance, not provided
- Y67H (p.Tyr67His), gnomAD 1-67169470-T-C, REVEL 0.63, CADD 21.90
- N69N (p.Asn69Asn), rs1306650296, gnomAD 1-67169478-T-C, CADD 4.14
- G70V (p.Gly70Val), ExAC rs759723554, gnomAD rs759723554, REVEL 0.38, CADD 17.40
- G70G (p.Gly70Gly), rs1425917268, gnomAD 1-67169481-C-T, CADD 6.42
- I71F (p.Ile71Phe), 1000Genomes rs576532413, ExAC rs576532413, TOPMed rs576532413, gnomAD rs576532413, REVEL 0.14, CADD 2.39
- I71V (p.Ile71Val), 1000Genomes rs576532413, ExAC rs576532413, TOPMed rs576532413, gnomAD rs576532413, REVEL 0.09, CADD 0.46, Uncertain significance, not specified
- K72R (p.Lys72Arg), gnomAD 1-67169486-A-G, REVEL 0.09, CADD 0.63
- E73Q (p.Glu73Gln), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- E73E (p.Glu73Glu), rs1171441053, gnomAD 1-67169490-A-G, CADD 6.38
- R74I (p.Arg74Ile), gnomAD rs1281925695, REVEL 0.43, CADD 13.20
- R74K (p.Arg74Lys), gnomAD rs1281925695, REVEL 0.19, CADD 1.94
- F75Y (p.Phe75Tyr), gnomAD rs1320853001, REVEL 0.15, CADD 0.13
- F75V (p.Phe75Val), gnomAD 1-67169494-T-G, REVEL 0.14, CADD 9.69
- F75L (p.Phe75Leu), gnomAD 1-67169494-T-C, REVEL 0.14, CADD 6.46
- Q76Q (p.Gln76Gln), gnomAD 1-67169499-A-G, CADD 0.02
- I77S (p.Ile77Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I77T (p.Ile77Thr), gnomAD rs1202465423, REVEL 0.27, CADD 8.50
- I77F (p.Ile77Phe), gnomAD 1-67169500-A-T, REVEL 0.32, CADD 9.64
- T78A (p.Thr78Ala), Ensembl rs558208409, REVEL 0.13, CADD 9.92
- T78K (p.Thr78Lys), gnomAD 1-67169504-C-A, REVEL 0.48, CADD 13.10
- R79K (p.Arg79Lys), NCI-TCGA Cosmic COSV6137, Variant assessed as somatic; moderate impact.
- R79R (p.Arg79Arg), rs368811377, gnomAD 1-67169508-G-A, CADD 6.93
- I80N (p.Ile80Asn), gnomAD 1-67169510-T-A, REVEL 0.68, CADD 24.40
- I80M (p.Ile80Met), gnomAD 1-67169511-T-G, REVEL 0.28, CADD 3.30
- I80I (p.Ile80Ile), rs138312673, gnomAD 1-67169511-T-A, CADD 1.35
- N81K (p.Asn81Lys), Ensembl rs1035929222, REVEL 0.47, CADD 21.30
- N81S (p.Asn81Ser), Ensembl rs1646915308, REVEL 0.40, CADD 23.30
- N81H (p.Asn81His), gnomAD 1-67169512-A-C, REVEL 0.48, CADD 23.90
- N81D (p.Asn81Asp), gnomAD 1-67169512-A-G, REVEL 0.47, CADD 24.30
- K82I (p.Lys82Ile), rs2525203281, ClinGen CA340732490, ClinVar RCV003578467, Uncertain significance, not provided
- K82N (p.Lys82Asn), rs1646915405, ClinGen CA340732491, ClinVar RCV001892412, TOPMed rs1646915405, MutPred 0.50, Uncertain significance, not provided
- K82Q (p.Lys82Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T84del (p.Thr84del), rs748507585, gnomAD 1-67169516-AAAC-A, CADD 16.60
- T84I (p.Thr84Ile), gnomAD 1-67169522-C-T, REVEL 0.52, CADD 20.40
- T84T (p.Thr84Thr), rs11465779, gnomAD 1-67169523-A-C, CADD 7.16
Public IL23R analysis runs
- IL23R analysis run — IL23R (888 variants) — completed 2026-08-21